The long-range objectives of the Colorado Learning Disabilities Research Center (CLDRC) are the identification, characterization, validation and amelioration of reading disabilities and ADHD, the two most prevalent and often co-morbid disorders of childhood. To accomplish these objectives, the CLDRC employs a unique approach that assesses the extent to which genetic and environmental influences underlie these disorders, and that uses covariation in etiology to understand whether deficits in component skills of reading are manifestations of a single syndrome or represent separate subtypes. Test batteries that include psychometric measures of cognitive and academic abilities (Project I), reading, writing, and language processes (Project II), and ADHD and executive functions (Project III) will be administered to a sample of identical and fraternal twins and their siblings in which at least one member of each twin pair has a reading disability, to an independent sample of twins and their siblings in which at least one member of each twin pair has ADHD, and to a comparison group of twins and their siblings with no school history of reading disabilities or ADHD. Resulting data will be used to assess the etiologies of reading deficits (including word recognition skills, reading fluency, comprehension, and writing), ADHD, and their comorbidity, as well as their covariation with measures of phoneme awareness, phonological decoding, orthographic coding, vocabulary, listening comprehension, and executive functions. In order to map quantitative trait loci that influence learning disabilities, and conduct association and mutation analyses, blood samples will be obtained from families of all twin pairs (Project IV). Project V will assess response to computer-assisted instruction in 3 samples: early (K-4th) at-risk readers, 2nd - 4th grade twins identified with reading disabilities in Projects l-lll, and 4th grade twins with reading disabilities for whom we have extensive longitudinal assessments starting from preschool. Response to instruction in project V will also be studied in the Project IV molecular-genetic analyses. An administrative core unit will be responsible for coordinating the activities of the five research projects, ascertaining and scheduling subjects, obtaining questionnaire data and blood samples, and administering the Center budget. Reading disabilities and ADHD are important public health problems. The proposed research will advance our understanding of their etiology and remediation.